Foggy thinking is a well-known side effect of cancer treatment, but is chemotherapy to blame?

Women who receive chemotherapy to treat breast cancer have long reported confusion, disorganization, difficulty concentrating and problems recalling conversations following therapy. And because these symptoms occur so soon after exposure to life-saving but toxic drugs, patients have assumed that so-called chemo brain is a direct result of the potent tumor-fighting drugs they have just received.

But in the latest study investigating the phenomenon, researchers led by Bernadine Cimprich, an associate professor emerita at the University of Michigan School of Nursing, says the changes in cognition actually occur before chemotherapy begins, and may worsen after treatment.

In a presentation at the annual CTRC-AACR San Antonio Breast Cancer Symposium, Cimprich reports that stress and fatigue related to receiving a cancer diagnosis and anticipating chemotherapy may be responsible for triggering muddled thinking. While previous studies have documented the phenomenon of chemo brain, this is the first to link the symptoms to fatigue and stress before treatment. She and her colleagues studied 28 women who received chemotherapy, 37 who received radiation, and 32 healthy controls without cancer. At the start of the study, all the participants completed verbal working memory tasks while their brains were scanned using functional MRI. They performed the same tasks one month after their chemotherapy or radiation treatment.

Even before any of the treatments began, Cimprich says the cancer patients scored lower on the memory tests than the healthy controls. There was a difference among the cancer patients as well, with those anticipating chemotherapy recording the lowest scores and those facing radiation treatment with slightly higher scores. These patterns continued after cancer treatment, with both chemotherapy and radiation patients showing worsening scores on the cognitive tests.

“We really don’t know what the independent effects of chemotherapy are,” says Cimprich. “What we are saying is that there are likely other factors that may be related to fatigue and worry, factors that start before any treatment, and are then compounded or enhanced by the effects of chemotherapy.”

For some reason, women waiting for chemotherapy showed the most deficits in cognitive functions, which suggests that anticipating the rigorous rounds of treatment and the potential side effects, including hair loss, nausea and vomiting, causes more psychological distress than concerns about radiation therapy.

The findings, in some ways, should be reassuring for breast cancer patients. Chemo brain is a serious enough concern for some women that it prevents them from getting treated, and while chemotherapy drugs likely have some effect on thinking, the possibility that anxiety and fatigue may play equally important roles in triggering those problems should provide some relief. That’s because these are issues that can be addressed with interventions such as meditation or relaxation exercises. “The study suggests the need to pay attention to fatigue and emphasizes for physicians something for us to work on with our patients,” says Dr. Claudine Isaacs, professor of medicine and Breast Cancer Program Clinical co-leader at Georgetown University. “There is no question that many women report changes in their short term memory recall, and find that they are not as sharp in their everyday tasks. But there are probably a lot of different factors that contribute to that, not just chemotherapy.”

Isaacs notes that in addition to the fatigue and stress associated with receiving a cancer diagnosis, the physiological change of menopause may also play a role. Chemotherapy can trigger menopause, which is associated with changes in memory and fuzzier thinking.

Cimprich plans to follow the women in the study for at least a year to answer other questions such as why some of them are more prone to the cognitive changes than others, and why the muddled thinking clears up relatively soon after chemotherapy for some. “We’re looking for a way to help, and maybe manage some of these problems a little better,” she says.